Display options
Cite
Le Noci V, Tortoreto M, Gulino A, et al. Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment. Oncoimmunology. 2015;4(10):e1040214doi: 10.1080/2162402X.2015.1040214.
Le Noci, V., Tortoreto, M., Gulino, A., Storti, C., Bianchi, F., Zaffaroni, N., Tripodo, C., Tagliabue, E., Balsari, A., & Sfondrini, L. (2015). Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment. Oncoimmunology, 4(10), e1040214. https://doi.org/10.1080/2162402X.2015.1040214
Le Noci, Valentino, et al. "Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment." Oncoimmunology vol. 4,10 (2015): e1040214. doi: https://doi.org/10.1080/2162402X.2015.1040214
Le Noci V, Tortoreto M, Gulino A, Storti C, Bianchi F, Zaffaroni N, Tripodo C, Tagliabue E, Balsari A, Sfondrini L. Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment. Oncoimmunology. 2015 May 27;4(10):e1040214. doi: 10.1080/2162402X.2015.1040214. eCollection 2015 Oct. PMID: 26451303; PMCID: PMC4589046.
Copy Download .nbib Format: NLM
Share it on

Oncoimmunology. 2015 May 27;4(10):e1040214. doi: 10.1080/2162402X.2015.1040214. eCollection 2015 Oct.

Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment.

Oncoimmunology

Valentino Le Noci, Monica Tortoreto, Alessandro Gulino, Chiara Storti, Francesca Bianchi, Nadia Zaffaroni, Claudio Tripodo, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini

Affiliations

  1. Dipartimento di Scienze Biomediche per la Salute; Università degli Studi di Milano ; Milan, Italy.
  2. Molecular Pharmacology Unit; Fondazione IRCCS Istituto Nazionale dei Tumori ; Milan, Italy.
  3. Dipartimento PRO.SA.MI; Unità di Immunologia dei Tumori; Universita degli Studi di Palermo ; Palermo, Italy.
  4. Molecular Targeting Unit; Fondazione IRCCS Istituto Nazionale dei Tumori ; Milan, Italy.
  5. Dipartimento di Scienze Biomediche per la Salute; Università degli Studi di Milano ; Milan, Italy ; Molecular Targeting Unit; Fondazione IRCCS Istituto Nazionale dei Tumori ; Milan, Italy.

PMID: 26451303 PMCID: PMC4589046 DOI: 10.1080/2162402X.2015.1040214

Abstract

The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases in C57BL/6 mice. Aerosolization of CpG-ODN with Poly(I:C) into the bronchoalveolar space reduced the presence of M2-associated arginase- and IL-10-secreting macrophages in tumor-bearing lungs and increased the antitumor activity of aerosolized CpG-ODN alone against B16 lung metastases without apparent signs of toxicity or injury of the bronchial-bronchiolar structures and alveolar walls. Moreover, CpG-ODN/Poly(I:C) aerosol combined with dacarbazine, a therapeutic agent used in patients with inoperable metastatic melanoma able to exert immunostimulatory effects, led to a significant increase in antitumor activity as compared to treatments with aerosolized CpG-ODN/Poly(I:C) or dacarbazine alone. This effect was related to an enhanced recruitment and cytotoxic activity of tumor-infiltrating NK cells in the lung. Our results point to aerosol delivery as a convenient approach for repeated applications of immunostimulants in patients with lung metastases to maintain a continuous local activation of innate immune cells while suppressing polarization of tumor-infiltrating macrophages to an M2 phenotype.

Keywords: TLR agonists; aerosol delivery; dacarbazin; lung metastases; mice

References

  1. Oncol Lett. 2012 Mar;3(3):613-616 - PubMed
  2. J Invest Dermatol. 2013 Feb;133(2):499-508 - PubMed
  3. Blood. 2012 Mar 29;119(13):3164-75 - PubMed
  4. Clinics (Sao Paulo). 2011;66(11):1879-86 - PubMed
  5. J Aerosol Med Pulm Drug Deliv. 2011 Dec;24(6):261-70 - PubMed
  6. Anticancer Drugs. 2007 Mar;18(3):291-6 - PubMed
  7. Clin Cancer Res. 2008 Sep 1;14(17):5512-8 - PubMed
  8. J Immunol. 2012 Mar 15;188(6):2509-15 - PubMed
  9. J Immunol. 2010 Sep 15;185(6):3481-8 - PubMed
  10. Cancer Res. 1985 Mar;45(3):1058-65 - PubMed
  11. Cancer Immunol Immunother. 2004 Aug;53(8):697-704 - PubMed
  12. Immunol Rev. 2008 Apr;222:357-68 - PubMed
  13. Pharm Res. 2011 Sep;28(9):2147-56 - PubMed
  14. J Thorac Oncol. 2010 Oct;5(10):1507-15 - PubMed
  15. J Exp Med. 2010 Nov 22;207(12):2675-87 - PubMed
  16. J Immunother. 2008 Jun;31(5):520-7 - PubMed
  17. Eur J Immunol. 2011 Sep;41(9):2522-5 - PubMed
  18. Hum Immunol. 2008 Aug;69(8):490-500 - PubMed
  19. J Innate Immun. 2014;6(3):293-305 - PubMed
  20. J Exp Clin Cancer Res. 2011 May 20;30:62 - PubMed
  21. Int J Cancer. 2013 Jul 15;133(2):383-93 - PubMed
  22. Eur Respir J. 2007 Oct;30(4):627-32 - PubMed
  23. J Immunother. 2012 Apr;35(3):245-53 - PubMed
  24. Pediatr Blood Cancer. 2014 Apr;61(4):618-26 - PubMed
  25. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2066-71 - PubMed
  26. J Invest Dermatol. 2013 Feb;133(2):289-92 - PubMed
  27. J Immunother. 2006 Sep-Oct;29(5):558-68 - PubMed
  28. Br J Cancer. 2013 Oct 1;109(7):1775-81 - PubMed
  29. J Immunol. 2012 Jun 1;188(11):5357-64 - PubMed
  30. J Aerosol Med Pulm Drug Deliv. 2013 Dec;26(6):345-54 - PubMed
  31. Immunotherapy. 2009 Nov;1(6):949-64 - PubMed
  32. Nature. 2005 Aug 25;436(7054):1186-90 - PubMed
  33. Int J Cancer. 2012 Aug 1;131(3):E227-35 - PubMed
  34. J Immunother. 2010 Jan;33(1):8-15 - PubMed

Publication Types